Radiofrequence ablation of liver cancers

Primary and secondary malignant liver cancer are some of most common malignant tumors in the world. Chemotherapy and radiotherapy are not very effective against them. Surgical resection has been considered the only potentially curtive option, but the majority of patients are not candidates for resection because of tumor size, location near major intrahepatic blood vessels and bile ducts, precluding a margin-negative resection, cirrhotic, hepatitis virus infection or multifocial. Radiofrequence ablation (RFA), which is a new evolving effective and minimally invasive technique, can produce coagulative necrosis of malignant tumors. RFA should be used percutaneously, laparascopically, or during the open laparotomy under the guidance of ultrasound, CT scan and MRI. RFA has lots of advantages superior to other local therapies including lower complications, reduced costs and hospital stays, and the possibility of repeated treatment. In general, RFA is a safe, effective treatment for unresectable malignant liver tumors less than 7.0 cm in diameter. We review the principle, mechanism, procedures and experience with RFA for treating malignant liver tumors.     

颅内外血栓在系统性红斑狼疮患儿中的发生情况比较*

目的 通过回顾性比较儿童系统性红斑狼疮（SLE）患者发生颅内、外血栓的情况,旨在发现SLE合并不同部位血栓的危险因素。方法 选取2006年1月—2019年12月首都医科大学附属北京儿童医院收治的SLE患儿,收集患儿人口学资料、临床表现、活动度评估及治疗、病程及随访资料等,并收集实验室检查数据及血栓相关数据等,根据血栓部位将患儿分为颅内血栓组及颅外血栓组,对两组资料进行比较。结果 27例SLE合并血栓患儿中,6例（22.22%）发生颅内血栓,21例（77.78%）患儿发生颅外血栓。颅内血栓以颅内静脉窦血栓形成（CVST）更为多见,横窦是CVST最常见的受累部位。颅外血栓常见受累部位依次为股总静脉、髂外静脉及股深浅静脉。颅外血栓组合并肾脏受累比例较颅内血栓组高（P?<0.05）,颅内血栓组合并神经系统受累比例较颅外血栓组高（P?<0.05）。颅外血栓组的Hb、C3、C4水平较颅内血栓组低,尿蛋白水平较颅内血栓组高（P?<0.05）。治疗后两组血栓均有一定程度的好转,其中颅内血栓组1例（16.7%）患儿血栓消失再通,颅外血栓组11例（52.4%）患儿血栓消失再通。结论 SLE合并颅内、外血栓形成有不同的特点,神经系统症状是颅内血栓最常见的症状,肾脏受累的患儿更易发生颅外血栓。早期诊断,积极治疗可明显改善SLE合并血栓患儿的预后。     

A new oxygen-rich energetic salt dihydrazine tetranitroethide: a promising explosive alternative with high density and good performance

A novel high-energy salt with good oxygen balance, dihydrazine tetranitroethide (5), has been synthesized and characterized by FT-IR spectroscopy, NMR spectroscopy, elemental analysis, and X-ray single crystal diffraction. Compound 5 exhibits high crystal density (1.81 g cm⁻³) and impressive detonation velocity (9508 m s⁻¹) and detonation pressure (37.9 GPa), showing potential applications as a high performance explosive and a promising additive of propellants.

A novel high-energy salt with good oxygen balance, dihydrazine tetranitroethide (5), has been synthesized and characterized by FT-IR spectroscopy, NMR spectroscopy, elemental analysis, and X-ray single crystal diffraction.

For applications in propellants, explosives and pyrotechnics, new energetic materials are required with high energy, insensitivity, high thermal stability and environment-friendly decomposition gases.¹ To achieve these goals, chemists have adopted a variety of strategies, such as construction of nitrogen-rich compounds,² energetic salts,³ metal organic framework (MOFs)⁴ and cage structure molecules.⁵ Oxygen balance (OB) is an important parameter to weigh the detonation performance of the nitrogen-rich compounds. Generally explosives may exhibit good performance when the OB close to zero.⁶ One conventional method of increasing the OB of energy materials is to introduce nitro groups, a typical high-energy and oxygen-rich substituent.⁷ Recently, gem-nitro and poly-nitro fragments, such as dinitromethyl,⁸ trinitroethyl⁹ and trinitromethyl,¹⁰ have been of interest to researchers. The compounds consisting of poly-nitro groups exhibit good OB, which largely improves their detonation velocities and pressures.¹¹ In our recent study,¹² we considered using tetranitroethylene instead of nitro as a pre-packaged module, linked to insensitive backbones, just like building blocks. The tetranitroethylene fragment has a high nitrogen content, a positive OB, and high energy within the molecule.¹³ The molecules consisting of the tetranitroethylene fragment are expected to be excellent energetic materials with superior properties.¹² But tetranitroethylene is an unstable intermediate, which is difficult to isolate.¹⁴ Hexnitroethane,¹⁵ a stable tetranitroethylene derivative, can be effectively used to synthetize poly-nitro bridged compound (Scheme 1). Previously, we discussed the possibility of constructing poly-nitro bridged-ring compounds with nitrogen-containing heterocycles and tetranitroethylene by using the Diels–Alder reaction.^12,16Open in a separate windowScheme 1Synthetic pathway for poly-nitro bridged compound.¹⁴Dipotassium tetranitroethide,¹⁷ another tetranitroethylene derivative, lead another thought to synthesize high energy salts with the tetranitroethane anion. The salt-based energetic materials often exhibit lower vapour pressure and higher densities than the non-ionic energetic materials.^3c In addition, the energetic salt can improve the properties by selecting different constituent ions.¹⁸ Based on the advantages of high-energy salt, we chose tetranitroethane anion and hydrazine cation to construct energetic salt by considering both energy and sensitivity. The synthetic route can be seen in Scheme 2. The good OB and large amounts of hydrogen-bonds prompt the target compound (dihydrazine tetranitroethide, 5) with suitable sensitivity and good performance. 5 possesses a crystal density of 1.81 g cm⁻³, detonation velocity of 9508 m s⁻¹ and detonation pressure of 37.9 GPa, which are higher than those of RDX. In addition, the salt-formation improves the carcinogenic and high toxic properties of hydrazine.Open in a separate windowScheme 2The route to synthesis of 5.The intermediate dipotassium tetranitroethide (3) was prepared from tetraiodoethylene (1) after two nitrification reactions, according to literature.¹⁹ The suspension of 3 in dichloromethane dissolves in concentrated sulfuric acid to give the solution of tetranitroethane (4) in dichloromethane. Treatment of the solution of 4 with hydrazine hydrate resulted in dihydrazine tetranitroethide (5), a yellow solid precipitated, that was confirmed by single crystal X-ray diffraction. Single crystal 5 is crystallized by using the method of the evaporation of water.Tetranitroethane 4 is also an unstable compound that is soluble in dichloromethane and difficult to isolate. It decomposed and released a brown gas as the solvent removed. Thus, we analysed the UV spectrum of the solution of 4, instead of the pure compound 4. Compared with the experimental and calculated UV spectrum of solution 4 (Fig. 1), we find that the maximum absorption wavelengths of the two curves match well, 240 nm (tested) and 239.5 nm (calculated). It can be inferred that compound 4 would be tetranitroethane.Open in a separate windowFig. 1The UV spectrum curve of tetranitroethane 4.Dihydrazine tetranitroethide 5 in the monoclinic space group C2/c with a good density of 1.81 g cm⁻³ (298 K). The gem-dinitro group is nearly planar, with the torsion angle of O5–N3–C2–N4, 179.52(17)°. However, the torsion angle of N3–C2–C2′–N4′ and N4–C2–C2′–N3′ are 77.57 (255)° and 77.57 (255)°, respectively, which shows the twist of adjacent dinitromethyl groups is caused by the steric effect. The strong hydrogen-bond interactions are presented between ammonium and nitro groups (Fig. 2b). The details of donor–acceptor distance are given in the ESI.^† Many studies have shown that the hydrogen-bonds enhance the stability of energetic molecules. At the molecular level, intermolecular hydrogen bonds between hydrazine cation and nitro groups play an important role in stabilizing energetic compounds. This kind of hydrogen-bonding interaction and cation–anion contact in the energetic salt is suggested as part of the explanation for closer packing, which causes the good density. As seen in Fig. 2c, the tetranitroethide anions are found in cross-stacking arrangements and layer by layer. While the hydrazine cation in the crystal, as the adhesive between the bricks, help to create a better stacking arrangement.Open in a separate windowFig. 2(a) Molecular structure of 5; (b) hydrogen-bonding interactions of 5 between hydrazine cation and tetranitroethide anion; (c) packing diagram of 5 (unit cell viewed along the b axis).The physical properties and calculated detonation performances are summarized in 20 Compound 5 has a detonation velocity of 9508 m s⁻¹ and a detonation pressure of P: 37.9 GPa, which is better than RDX (8748 m s⁻¹; 34.9 GPa) and similar to HMX (9320 m s⁻¹; 39.5 GPa). The sensitivities to impact and friction are 1.25 J and 34 N, respectively.Physical properties of dihydrazine tetranitroethide 5 and comparison with ADN, RDX and HMX

Amelioration in Hepatic Insulin Sensitivity by Reduced Hepatic Lipid Accumulation at Short-Term After Roux-en-Y Gastric Bypass Surgery in Type 2 Diabetic Rats

Background

Previous studies showed that early after Roux-en-Y gastric bypass (RYGB), there is a remarkable improvement in type 2 diabetes, which is characterized by insulin resistance. This study aims to gain insight into the underlying mechanisms of this effect. We determined the acute effects of RYGB on hepatic and peripheral insulin sensitivity.

Methods

A rat model of type 2 diabetes was established using high-fat diet combined with streptozotocin (30 mg/kg, ip). Animals were divided into four groups: diabetic, diabetic RYGB, diabetic RYGB sham, and control rats. Hyperinsulinemic-euglycemic clamps with tracer infusion were completed at 2 weeks postoperatively to assess insulin sensitivity. Triglyceride concentration in liver and muscle tissues was determined. Protein kinase C (PKC) membrane translocation, protein expression of phospho-c-Jun NH₂-terminal kinase (JNK), and phospho-IκB kinase β (IKKβ) were assessed with western blot. Malondialdehyde (MDA) and superoxide dismutase (SOD) activities in the liver were also measured.

Results

RYGB surgery significantly improved hepatic insulin sensitivity index and decreased hepatic triglyceride concentration (P?<?0.05), without an improvement in peripheral insulin sensitivity. Membrane translocation of PKC-ε, PKC-δ, and PKC-θ; the ratio of MDA to SOD; and the expression of p-JNK and p-IKKβ in the liver were lower in the diabetic RYGB group than in the diabetic group.

Conclusions

Diabetes remission was induced at short term after RYGB. The improvement of hepatic tissue lipotoxicity decreased the activation of certain PKC isoforms, the activity of JNK and IKK inflammatory signaling pathways, and the degree of oxidative stress. Furthermore, the hepatic insulin sensitivity was ameliorated, which is possibly a mechanism for early diabetes remission.     

Dose rectification of an imbalance between DPP4 and GLP‐1 ameliorates chronic stress‐related vascular aging and atherosclerosis?

Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Dipeptidyl peptidase‐4 (DPP‐4) exerts many physiological and pharmacological functions by regulating its extremely abundant substrates [eg., glucagon‐like peptide‐1 (GLP‐1), stromal cell‐derived factor‐1α/C‐X‐C chemokine receptor type‐4, etc.]. Over the past decade, emerging data has revealed unexpected roles for DPP‐4 and GLP‐1 in intracellular signaling, oxidative stress production, lipid metabolism, cell apoptosis, immune activation, insulin resistance, and inflammation. This mini review focuses on recent findings in this field, highlighting an imbalance between DPP4 and GLP‐1 as a potential therapeutic target in the management of vascular aging and atherosclerosis in animals under experimental stress conditions.     

Foot care knowledge,attitudes and practices among patients with diabetic foot and amputation in St. Kitts and Nevis

About one‐third of admissions to the surgical unit annually are diabetes foot infections in need of amputation In St. Kitts and Nevis. However, the risk factors related to diabetes foot and amputation remain unknown. This study investigated factors associated with diabetic foot and amputation (DFA). Retrospective case control study design, and purposive and quota sampling method was used to recruit the participants. Patients with and without DFA were interviewed at two main hospitals, several primary health centres, and a private doctor's office during July and August 2018. Self‐development questionnaires were applied to assess patients' demographic, physical and behaviour, foot care knowledge, attitudes, and practices related to DFA. Chi‐square, t‐test, and multiple logistic regressions were used to analyse the data. A total of 210 patients were evaluated, 89 had DFA, while 121 did not, with a mean age of 61.10 (SD = 11.85). Participants' responses indicated good knowledge, favourable attitudes, and adequate practices related to foot care. The two items of the questionnaire, ways to maintain blood flow in the lower extremities and wash their feet daily, had significant lower score in DFA group. In multiple logistic regression, knowledge, attitudes, and practices related to foot care were not a significant predictor of DFA. Being male was a predictor of DFA than female (OR = 3.53; 95% CI = 1.65‐7.57; P < .01). Participants who were currently unemployed were less likely to have DFA than those who were employed (OR = 0.38; 95% Cl = 0.17‐0.86; P < .05). Comparing patients with the longest experience of diabetes mellitus (31 years or more) with those who had diabetes for the shortest period of time (between 1 and 10 years) was less likely to have DFA (OR = 0.38; 95% CI = 0.15‐0.97; P = <.05). The combination of these independent variables could explain 29% of the variance in DFA. Based on these findings, strategies to prevent diabetic foot and amputation should focus on male and outdoor heavy worker, and longer duration of diabetes patients which are identified in this study.